Published online 15 October 2010 | Nature | doi:10.1038/news.2010.544

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Stem-cell papers under suspicion

Duplicate plots may be at issue in a retracted stem-cell study.

Plots from two different experiments that seem to be nearly identical to one another are here presented together for comparison. The upper plot is from supplementary Figure S3b, associated with a recently retracted Nature paper by Mayack et al. (Nature 463, 495–500; 2010). The lower plot is part of Figure 6c from an earlier paper by Mayack and Wagers in the journal Blood (Blood 112, 519-531; 2008). The plots chart the frequency of blood stem cells in two different experimental situations, based on the detection of the sca-1 and c-kit markers.

A day after a high-profile stem-cell paper published earlier this year was retracted from Nature, editors of a second journal, Blood, have posted a 'notice of concern' regarding a 2008 paper from the same lab. A comparison of the papers made by Nature reporters has revealed two pairs of flow cytometry plots that seem to be duplicates.

The retracted paper, which was cited 13 times, according to the Web of Science online citation index, describes a series of experiments — including stitching together the circulatory systems of old and young mice — to show that age-related changes in adult blood stem cells can be influenced and even reversed by their environment1.

The first author of both papers, Shane Mayack, was a postdoc in the lab of Amy Wagers, a researcher at Harvard Medical School's Joslin Diabetes Center in Boston, Massachusetts, until 1 October.

In a retraction notice published in Nature yesterday2, Wagers and the paper's two other authors wrote that "a re-examination of the publication raised serious concerns with some of the reported data", and has "undermined the authors' confidence in the support for the scientific conclusions reported". It also noted that Mayack, who did not sign the retraction, "maintains that the results are still valid".

Mayack and Wagers are the sole authors on the Blood paper, which examines the role of bone cells in regulating blood stem cells3. "As a result of an internal review by the corresponding author, serious concerns with some of the reported data were raised," the notice in Blood says. "This matter is currently under further review. Blood will inform the readers of the outcomes."

Correcting the record

Wagers noted in an e-mailed statement to Nature that she was alerted to information that undermined her confidence in the Nature paper's conclusions and immediately informed the journal, Joslin Diabetes Center and Harvard Medical School. "The integrity of the scientific process and my research is my highest priority, and I have acted to ensure that any errors in the record are fully corrected," she wrote.

Both she and the university declined to comment on whether a formal investigation was under way or on the seemingly duplicated images.

The two plots in the Nature paper show flow cytometry data — a counting up of cells — after exposure to other cells in bone marrow taken from younger and older mice. They appear in Figure S3b in the supplementary material of the Nature paper. Two nearly identical plots showing cell counts after exposure to osteoblasts (bone cells) lacking a particular protein appear in Figure 6c of the Blood paper.

Mayack did not respond directly to enquiries from Nature, but her lawyer provided the following statement:

Dr. Mayack acknowledges that errors were made in assembling the figures for the manuscripts. She firmly believes, however, that the underlying data fully support the main conclusions of the Nature article as published. For this reason, she did not sign the retraction. Dr. Mayack apologizes for any inconvenience this has caused her colleagues.

What the retraction means for the field remains to be seen, stem-cell researchers say.

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"I thought that was a very interesting and important result," says Norman Sharpless, who studies stem cells and ageing at the University of North Carolina School of Medicine. "One wonders if the result is wrong or just not conclusively proven."

"The study itself was incredibly exciting because it suggested that there are circulating factors that could play a role in influencing the ageing process of blood stem cells," says Kenneth Chien, a stem-cell researcher also at Harvard Medical School who was not involved in either paper. "There's clearly a strong link between ageing and stem-cell renewal, and this paper went a long way towards suggesting that a circulating factor could play a role."

Chien applauded Wagers' decision to retract it, however, stressing it doesn't mean the result should be dismissed. "Amy's response is entirely appropriate – it takes this off the table but it doesn't necessarily mean the concept is wrong. It does mean it needs to be more rigorously examined," he says. 

  • References

    1. Mayack, S.R., et al., Nature 463:495-501 (2010)
    2. Mayack, S.R., et al., Nature doi:10.1038/nature09474 (2010)
    3. Mayack, S.R., and Wagers, A.J., Blood 112: 519-531 (2008)

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  • #60887

    I would say that, certainly for me, the too good to be true effect usually outweighs the awe-struck effect for papers making extraordinary claims.

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